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Gene Expression Profiling Reveals Similarities between the In vitro and In vivo Responses of Immune Effector Cells to IFN-

Authors' Affiliations: ¹ Integrated Biological Sciences Graduate Program, ² Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, ³ Department of Internal Medicine, ⁴ Center for Biostastistics, and ⁵ Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio

Requests for reprints: William E. Carson III, Department of Surgery, The Ohio State University, N924 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210. Phone: 614-293-6306; Fax: 614-293-3465; E-mail: william.carson{at}osumc.edu.

Purpose: The precise molecular targets of IFN- therapy in the context of malignant melanoma are unknown but seem to involve signal transducers and activators of transcription 1 signal transduction within host immune effector cells. We hypothesized that the in vitro transcriptional response of patient peripheral blood mononuclear cells (PBMC) to IFN- would be similar to the in vivo response to treatment with high-dose IFN-.

Experimental Design: The gene expression profiles of PBMCs and immune cell subsets treated in vitro with IFN- were evaluated, as were PBMCs obtained from melanoma patients receiving adjuvant IFN-.

Results: Twenty-seven genes were up-regulated in PBMCs from normal donors after treatment with IFN- in vitro for 18 hours (>2-fold, P < 0.001). A subset of these genes (in addition to others) was significantly expressed in IFN-–treated T cells, natural killer cells, and monocytes. Analysis of gene expression within PBMCs from melanoma patients (n = 13) receiving high-dose IFN--2b (20 MU/m² i.v.) revealed significant up-regulation (>2-fold) of 21 genes (P < 0.001). Also, the gene expression profile of in vitro IFN-–stimulated patient PBMCs was similar to that of PBMCs obtained from the same patient after IFN- therapy.

Conclusions: This report is the first to describe the transcriptional response of T cells, natural killer cells, and monocytes to IFN- and characterize the transcriptional profiles of PBMCs from melanoma patients undergoing IFN- immunotherapy. In addition, it was determined that microarray analysis of patient PBMCs after in vitro stimulation with IFN- may be a useful predictor of the in vivo response of immune cells to IFN- immunotherapy.